RU2750199C2 - Compositions containing zink phosphate - Google Patents

Abstract

FIELD: oral care products.

SUBSTANCE: invention relates to the field of oral care products. The proposed dentifrice contains from 1 to 3% by weight of zinc phosphate, where zinc phosphate is added to the dentifrice as a preformed salt, arginine in free or orally acceptable salt form in an amount of 1 to 8% by weight, from 2 to 8% by weight of an alkaline phosphate salt selected from sodium phosphate dibasic, potassium phosphate dibasic, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and a mixture of any two or more of these, from 700 to 2000 ppm fluoride-based dentifrice with a silicon dioxide-based abrasive.

EFFECT: use of the above composition provides improved zinc deposition and enamel acid exposure protection compared to compositions containing arginine and zinc citrate.

6 cl, 3 tbl, 4 ex

Description

BACKGROUND OF THE INVENTION

Dental erosion involves demineralization and damage to the structure of the teeth due to acid attack from non-bacterial sources. Erosion is detected first in the enamel and, if it is not stopped, it can pass into the dentin underneath. Dental erosion can be caused or worsened by acidic foods and drinks, exposure to chlorinated pool water, and regurgitation of stomach acid. Tooth enamel is a negatively charged surface that naturally attracts positively charged ions such as calcium and hydrogen ions while resisting negatively charged ions such as fluoride ions. Depending on the relative pH of the surrounding saliva, tooth enamel loses or gains positively charged ions such as calcium ions. Saliva usually has a pH between 7.2 and 7.4. When the pH drops and the concentration of hydrogen ions becomes relatively high, hydrogen ions will replace calcium ions in the enamel, forming acid phosphate (phosphoric acid), which damages the enamel and creates a porous, spongy, rough surface. If saliva remains acidic for an extended period of time, remineralization may not occur and the tooth will continue to lose minerals, causing the tooth to weaken and eventually lose structure.

There is a need for improved products for treating and reducing erosion.

Heavy metal ions such as zinc are resistant to acid attack. Zinc is higher than hydrogen in the electrochemical series of potentials, so that metallic zinc in an acidic solution will react with the evolution of hydrogen, since zinc goes into solution in the form of dication, Zn ²⁺ . In the study of plaque and caries, zinc has been shown to have antibacterial properties.

Soluble zinc salts such as zinc citrate have been used in dentifrice compositions but have several disadvantages. Free zinc ions can react with fluoride ions to form zinc fluoride, which is insoluble and therefore reduces the bioavailability of both zinc and fluoride. In addition, zinc ions in solution impart an unpleasant, astringent taste, so it has been difficult to obtain formulations that provide effective zinc levels as well as acceptable organoleptic properties. Finally, zinc ions react with anionic surfactants such as sodium lauryl sulfate, thereby inhibiting foaming and cleaning.

Zinc phosphate (Zn ₃ (PO ₄ ) ₂ ) is insoluble in water, despite being soluble in acidic or basic solutions, for example, solutions of mineral acids, acetic acid, ammonia or alkali metal hydroxides. See, for example, Merck Index, 13th Ed. (2001) p. 1812, monograph number 10205. Partly because it is perceived in the art as a generally inert material, it is widely used in dental cements, for example, in the cementation of inlays, crowns, bridges and orthodontic appliances. which are designed to be in the mouth for many years. Zinc phosphate dental cements are generally prepared by mixing zinc oxide and magnesium oxide powders with a liquid consisting mainly of phosphoric acid, water, and buffers so that the zinc phosphate cement is formed in situ by reaction with phosphoric acid.

Summary

It has been found that zinc phosphate, when placed in a formulation, for example at acidic or alkaline pH, can sufficiently dissolve when used to provide an effective concentration of zinc ions in enamel, thereby contributing to erosion protection, reducing bacterial colonization and biofilm development. and providing enhanced shine to the teeth. In some embodiments, amino acids are included in the formulation, eg, basic amino acids, eg, arginine or lysine, which can provide an alkaline pH to the formulation. In addition, it has been found that zinc phosphate formulated with a second phosphate source enhances phosphate precipitation. This is all surprising given the poor solubility of zinc phosphate and the prevailing opinion in the art that it is substantially inert in the oral cavity, as evidenced by its widespread use in dental cement. At the same time, formulations containing zinc phosphate do not exhibit poor taste and mouthfeel, poor fluoride delivery, and poor foaming and cleansing associated with conventional zinc-based oral care products that use more soluble zinc salts.

Thus, the invention provides oral compositions such as dentifrices that contain zinc phosphate. In some embodiments, zinc phosphate is added to dentifrices as a preformed salt. In one embodiment, the composition further comprises an amino acid, eg, a basic amino acid. The compositions may optionally further comprise a fluoride source and / or an additional phosphate source. The compositions can be formulated as a conventional dentifrice or mouthwash, for example, containing abrasives such as silica abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, antimicrobials , preservatives, flavors, colors and / or combinations thereof. For example, in one embodiment, the invention provides a dentifrice comprising about 2% zinc phosphate, about 5% arginine, about 5% alkaline phosphate salts, and about 1450 ppm fluoride, in a dentifrice base with a dioxide abrasive silicon.

The invention further provides methods of using the compositions of the invention for reducing and suppressing acid erosion of enamel, cleaning teeth, reducing bacterial biofilm and plaque, reducing gum inflammation, inhibiting caries and cavities, and reducing dentinal hypersensitivity, comprising brushing teeth with the composition according to the invention.

Additional areas of applicability of the present invention will become apparent from the detailed description provided below. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

DETAILED DESCRIPTION

The following description of the preferred embodiment (s) is merely exemplary in nature and is in no way intended to limit the invention, its application or use.

As used herein, the term "preformed salt" when used in relation to zinc phosphate means that zinc phosphate is not formed in situ in the dentifrice or mouthwash, for example, by the reaction of phosphoric acid and zinc salt ...

Thus, the invention provides, in a first embodiment, an oral composition for occasional use, such as daily use, such as a dentifrice or mouthwash, containing zinc phosphate (composition 1), for example,

1.1. Dentifrice composition 1 comprising zinc phosphate in a dentifrice base, for example, wherein the zinc phosphate is present in an effective amount, for example, in an amount of 0.5 to 4% by weight, for example, from about 1 to 3 % by weight based on dentifrice.

1.2. Composition 1.1, wherein the dentifrice base contains an effective amount of a silica abrasive, for example 10-30%, for example about 20%.

1.3. Composition 1 in the form of a mouthwash containing zinc phosphate, for example, in an amount of 0.005 to 0.05% by weight, for example, about 0.01-0.03% by weight, in a mouthwash base.

1.4. Any of the foregoing compositions further comprising an effective amount of a fluoride ion source, for example providing 500 to 3000 ppm fluoride.

1.5. Any of the foregoing compositions further comprising an effective amount of fluoride, for example, wherein the fluoride is a salt selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, aminofluoride (for example, N'-octadecyltrimethylenediamine-N , N'-tris (2-ethanol) -difluorohydrate), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

1.6. Any of the foregoing compositions containing an amino acid in an amount sufficient to increase the solubility of zinc phosphate, for example, from about 0.5 wt% to about 20 wt% based on the total weight of the composition, from about 0.5 wt% to about 10 wt% .% of the total weight of the composition, for example, about 1.5 wt.%, about 3.75 wt.%, about 5 wt.%, or about 7.5 wt.% of the total weight of the composition in the case of a dentifrice, or for example about 0.5-2% by weight, for example about 1% in the case of a mouthwash.

1.7. Any of the above compositions containing a basic amino acid, for example, arginine or lysine, or combinations thereof, for example, l-arginine, for example, in an effective amount, for example, in an amount effective in combination with zinc phosphate to reduce erosion, dentinal hypersensitivity and / or accumulation of plaque, for example, in an amount of about 1-10% of the total weight of the composition in the case of a dentifrice, or for example, about 0.5-2 wt.%, for example, about 1% in the case of a mouthwash.

1.8. Any of the preceding compositions containing a basic amino acid, eg arginine, in an amount sufficient to raise the pH of the composition above pH 8, eg, to pH 8.5-10.

1.9. Any of the preceding compositions further comprising additional sources of zinc ions, for example selected from zinc citrate, zinc sulfate, zinc silicate, zinc lactate, zinc oxide, and combinations thereof; for example, in one embodiment, a dentifrice comprising 1% zinc phosphate and 1% zinc citrate.

1.10. Any of the preceding compositions containing an effective amount of one or more alkaline phosphate salts, for example sodium, potassium or calcium salts, for example selected from alkaline dibasic phosphate and alkaline pyrophosphate salts, for example alkaline phosphate salts selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate and mixtures of any two or more of these, for example, in an amount of 1-20%, for example, 2-8%, for example, about 5% by weight of the composition ...

1.11. Any of the above compositions containing buffering agents, for example, sodium phosphate buffered saline (for example, sodium phosphate monobasic and disodium phosphate).

1.12. Any of the above compositions containing a humectant, for example, selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, for example containing at least 20%, for example 20-40%, for example 25-35% glycerin ...

1.13. Any of the preceding compositions containing one or more surfactants, for example, selected from anionic, cationic, zwitterionic and nonionic surfactants and mixtures thereof, for example, comprising an anionic surfactant, for example, a surfactant selected from sodium lauryl sulfate, sodium lauryl ether sulfate and mixtures thereof, for example, in an amount of from about 0.3% to about 4.5% by weight, for example, 1-2% sodium lauryl sulfate (SLS); and / or zwitterionic surfactants, for example, a surfactant based on betaine, for example, cocamidopropyl betaine, for example, in an amount of from about 0.1% to about 4.5% by weight, for example, 0.5 -2% cocamidopropyl betaine.

1.14. Any of the preceding compositions further comprising a viscosity-modifying amount of one or more of a polysaccharide gum such as xanthan gum or carrageenan, a silica thickener, and combinations thereof.

1.15. Any of the preceding compositions comprising wafers or gum fragments.

1.16. Any of the preceding compositions further comprising a fragrance, flavor, and / or colorant.

1.17. Any of the above compositions containing an effective amount of one or more antibacterial agents, for example, containing an antibacterial agent selected from halogenated diphenyl ether (for example, triclosan), herbal extracts and essential oils (for example, rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, quinokitol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, misvak extract, sea buckthorn extract, bisguanide antiseptics (for example, chlorhexidinium chloride) CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl sulphate-4-ethylpyridinium chloride (TDEPC)), phenolic antiseptics, hexetidine, octenidine, sanguinarine, povidoniodine, delmopintrain, metal ions, salifluoro zinc, tin fluoride salts, copper salts, salts iron), sanguinarine, propolis and oxidizing substances (for example, hydrogen peroxide, buffered peroxyborate or sodium peroxycarbonate), phthalic acid and its salts, monoperphthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, domoccinyl methylophthalate, octafinol and other piperidine derivatives, nicine preparations, chlorite salts; and mixtures of any of the above; for example, including triclosan or cetylpyridinium chloride.

1.18. Any of the above compositions comprising an antibacterially effective amount of triclosan, for example 0.1-0.5%, for example about 0.3%.

1.19. Any of the preceding compositions further comprising a whitening agent, for example selected from the group consisting of metal peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof.

1.20. Any of the preceding compositions further comprising hydrogen peroxide or a source of hydrogen peroxide, for example, carbamide peroxide or a salt or peroxide complex (for example, such as salts of peroxyphosphate, peroxycarbonate, perborate, peroxysilicate or persulfate; for example, calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate and potassium persulfate);

1.21. Any of the preceding compositions further comprising an agent that inhibits or prevents bacterial attachment, such as solbrol or chitosan.

1.22. Any of the preceding compositions further comprising a calcium and phosphate source selected from (i) calcium-glass complexes, for example calcium sodium phosphosilicates, and (ii) calcium-protein complexes, for example casein phosphopeptide-amorphous calcium phosphate.

1.23. Any of the preceding compositions further comprising a soluble calcium salt, for example selected from calcium sulfate, calcium chloride, calcium nitrate, calcium acetate, calcium lactate, and combinations thereof.

1.24. Any of the preceding compositions further comprising a physiologically or orally acceptable potassium salt, for example potassium nitrate or potassium chloride, in an amount effective to reduce dentinal sensitivity.

1.25. Any of the above compositions further comprising an anionic polymer, eg, a synthetic anionic polymer polycarboxylate, eg, wherein the anionic polymer is selected from 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer; for example, where the anionic polymer is a methyl vinyl ether / maleic anhydride copolymer (PVM / MA) having an average molecular weight (M.W.) from about 30,000 to about 1,000,000, such as from about 300,000 to about 800,000, for example, where the anionic polymer constitutes about 1-5%, for example, about 2% by weight of the composition.

1.26. Any of the preceding compositions further comprising a breath freshener, fragrance, or fragrance.

1.27. Any of the above compositions, wherein the pH of the composition is acidic or basic, for example, from pH 4 to pH 5.5, or from pH 8 to pH 10.

1.28. Any of the above compositions, which is a dentifrice, wherein the composition comprises

1-3%, for example about 2% zinc phosphate;

2-8%, for example about 5% L-arginine (free base);

2-8%, for example about 5% alkaline phosphate salts, for example selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any two or more of these;

700-2000 mg, for example about 1450 ppm fluoride, for example 0.3-0.4%, for example about 0.32% sodium fluoride;

in the basis of a dentifrice with an abrasive based on silicon dioxide.

1.29. Any of the above compositions, which is a mouthwash, wherein the composition comprises

5-10%, for example about 7.5% glycerin;

3-7%, for example about 5.5% sorbitol;

5-10%, for example about 7% propylene glycol;

0-0.1% TSPP;

0.01-1% sweetener, such as about 0.02% saccharin;

0.01-1%, for example, about 0.05% citric acid;

0-0.1% xanthan;

0.005-0.05%, for example about 0.028% zinc phosphate;

0-0.01% cetylpyridinium chloride;

0.01-0.1%, for example about 0.05% potassium sorbate;

0.05-1%, such as about 0.1-0.2% flavor;

0.1-2%, for example about 1% cocamidopropyl betaine;

Water (optionally along with any additional ingredients) to replenish the balance, for example about 70-85%, for example about 80% water.

1.30. Any of the above compositions containing the same ingredients as in the tested formulation of Example 1 or Example 4 below.

1.31. Any of the preceding compositions effective when applied to the oral cavity, for example using a brush, to (i) reduce tooth hypersensitivity, (ii) reduce plaque buildup, (iii) reduce or prevent demineralization and promote tooth remineralization, (iv) suppressing microbial biofilm formation in the oral cavity, (v) reducing or suppressing gingivitis, (vi) to accelerate healing of sores or cuts in the mouth, (vii) to decrease levels of acid producing bacteria, (viii) to increase relative levels of non-caries and / or non-plaque-forming bacteria, (ix) reduce or inhibit the formation of dental caries, (x) reduce, heal, or suppress precarious enamel lesions, for example, as identified by quantitative photoinduced fluorescence (QLF) or electrical caries measurement (ECM), (xi) treating, relieving or reducing dry mouth, (xii) cleaning teeth and mouth, (xiii) reducing erosion, (xiv) o whitening of teeth; and / or (xv) promoting systemic health, including cardiovascular health, for example, by reducing the potential for systemic infection through oral tissues.

1.32. Compositions obtained or obtained by combining ingredients specified in any of the preceding compositions.

The invention further provides for the use of zinc phosphate in the manufacture of an oral care composition such as a dentifrice and methods for increasing the level of zinc in enamel. In some embodiments, zinc phosphate is added to the dentifrice as a preformed salt.

The invention also provides methods of using the compositions of the invention to increase zinc levels in enamel and to treat, reduce or control the occurrence of enamel erosion, comprising applying the composition as described above, for example, any of Composition 1 and subsequent, to teeth, for example, with a brush ... In various embodiments, the invention provides (i) reducing tooth hypersensitivity, (ii) reducing plaque accumulation, (iii) reducing or preventing demineralization and promoting tooth remineralization, (iv) suppressing microbial biofilm formation in the oral cavity, (v) reducing or inhibiting gingivitis, (vi) accelerating the healing of sores or cuts in the mouth, (vii) decreasing the levels of acid-producing bacteria, (viii) increasing the relative levels of non-caries and / or non-plaque bacteria, (ix) reducing or suppressing the formation of dental caries , (x) reducing, healing, or suppressing precarious enamel lesions, such as those identified by quantitative photoinduced fluorescence (QLF) or electrical caries measurement (ECM), (xi) treating, alleviating or reducing dry mouth, (xii) cleaning teeth and cavities mouth, (xiii) erosion reduction, (xiv) teeth whitening; and / or (xv) preventing tartar buildup and (xvi) promoting systemic health, including cardiovascular health, for example, by reducing the potential for systemic infection through oral tissues, comprising using any of Compositions 1 and the following as described above, for the oral cavity of a person in need thereof, for example, by brushing the teeth one or more times a day, any of Composition 1 and the following. The invention also provides Compositions 1 and the following for use in any of these methods.

Active Ingredients : The compositions of the invention may include various substances that are active to protect and increase the strength and integrity of enamel and tooth structure and / or to reduce bacteria and associated caries and / or gum disease. The effective concentration of the active ingredients used herein will depend on the specific substance and the delivery system used. It should be understood that a dentifrice, for example, is typically diluted with water upon use, whereas a mouthwash is typically not diluted. Thus, the effective concentration of active substances in a toothpaste is usually 5-15 times higher than that required for rinsing the mouth. The concentration also depends on the exact salt or polymer selected. For example, if the active agent is in the form of a salt, the counterion will affect the weight of the salt, so if the counterion is heavier, more salt (by weight) will be required to provide the same active ion concentration in the final product. Arginine, where present, can be present at levels from, for example, about 0.1 to about 20 wt% (expressed as weight of the free base), for example, from about 1 to about 10 wt% for a consumer toothpaste, or from about 7 to about 20% by weight for a professional product or a product for a recommended treatment. Fluoride, if present, may be present at levels of, for example, about 25 to about 25,000 ppm, such as about 750 to about 2,000 ppm for a consumer toothpaste, or about 2,000 to about 25,000 ppm for a professional product or product. for the recommended treatment. The levels of antibacterial agents will vary similarly to those used in toothpaste, for example, about 5 to about 15 times those used for rinsing the mouth. For example, a triclosan dentifrice can contain about 0.3% by weight triclosan.

Fluoride Ion Source : Oral compositions may additionally include one or more fluoride ion sources, such as soluble fluoride salts. A wide variety of fluoride ion-providing materials can be used as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-providing materials are found in US Pat. No. 3,535,421 to Briner et al .; US patent No. 4885155, Parran, ml. et al. and US Pat. No. 3,678,154 to Widder et al. Representative sources of fluoride ions include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, aminofluoride, ammonium fluoride, and combinations thereof. In some embodiments, the fluoride ion source includes stannous fluoride, sodium fluoride, sodium monofluorophosphate, and mixtures thereof. In some embodiments, an oral composition of the invention may also contain a source of fluoride ions or fluorine-providing ingredients in amounts sufficient to provide from about 25 ppm to about 25,000 ppm fluoride ions, typically at least at least about 500 ppm, for example, about 500 to about 2000 ppm, for example, about 1000 to about 1600 ppm, for example, about 1450 ppm. The appropriate fluoride level will depend on the specific application. Toothpaste for general household use typically contains between about 1000 and about 1500 ppm, while children's toothpaste contains slightly less. A dentifrice or coating for professional use can contain up to about 5,000 ppm or even about 25,000 ppm fluoride. Sources of fluoride ions can be added to compositions of the invention at a level of from about 0.01 wt% to about 10 wt% in one embodiment, or from about 0.03 wt% to about 5 wt% and in another embodiment implementation from about 0.1 wt.% to about 1 wt.% in another embodiment. The weights of the fluoride salts to provide the correct level of fluoride ions will obviously vary with the weight of the counterion in the salt.

Amino Acids : In some embodiments, the compositions of the invention comprise an amino acid. In specific embodiments, the amino acid may be a basic amino acid. By "basic amino acid" is meant naturally occurring basic amino acids such as arginine, lysine and histidine, as well as any basic amino acids having a carboxyl group and an amino group in a molecule that is water-soluble and provides an aqueous solution of about 7 or higher. Accordingly, basic amino acids include, but are not limited to, arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminopropionic acid, salts thereof, or combinations thereof. In a specific embodiment, the basic amino acids are selected from arginine, citrulline, and ornithine. In some embodiments, the basic amino acid is arginine, for example l-arginine or a salt thereof. In other embodiments, the amino acid is quaternized, i. E. the amino group is further substituted to form a quaternary ammonium moiety which can form an internal salt with a carboxyl group, eg betaine (N, N, N-trimethylglycine).

In various embodiments, the amino acid is present in an amount from about 0.5 wt% to about 20 wt% based on the total weight of the composition, from about 0.5 wt% to about 10 wt% based on the total weight of the composition, for example, about 1 , 5 wt.%, About 3.75 wt.%, About 5 wt.% Or about 7.5 wt.% Based on the total weight of the composition in the case of a dentifrice, or, for example, about 0.5-2 wt. %, for example, about 1% in the case of a mouthwash.

Abrasives : Compositions according to the invention, for example, Composition 1 and trace. include abrasives based on silicon dioxide, and may contain additional abrasives, for example, abrasives based on calcium phosphate, for example tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ ), hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) or dicalcium phosphate dihydrate (CaHPO ₄ ⋅ 2H ₂ O, also sometimes called DiCal) or calcium pyrophosphate; abrasive based on calcium carbonate; or abrasive materials such as sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite, or other siliceous materials, or combinations thereof.

Other silicon dioxide abrasives used herein, as well as other abrasives, typically have an average particle size in the range of about 0.1 to about 30 microns, from about 5 to about 15 microns. The silica abrasives can be precipitated silica or silica gels such as the silica xerogels described in US Pat. No. 3,538,230 to Pader et al. and US Pat. No. 3,862,307 to Dugiulio. Specific silica xerogels are marketed under the trade name Syloid® from W. R. Grace & Co., Davison Chemical Division. Precipitated silica materials include materials from J. M. Huber Corp. marketed under the trade name Zeodent®, including silica bearing the designation Zeodent 115 and 119. These silica abrasives are described in US Pat. No. 4340583 to Wason. In some embodiments, abrasives useful in the practice of compositions for caring for the oral cavity in accordance with the invention include silica gels and precipitated amorphous silica having an oil absorption coefficient of less than 100 cc. cm / 100 g of silicon and in the range from about 45 cc. cm / 100 g to about 70 cc cm / 100 g of silicon dioxide. The oil absorption index is determined using the ASTA Rub-Out Method D281. In certain embodiments, silicas are colloidal particles having an average particle size of from about 3 microns to about 12 microns and from about 5 to about 10 microns. Low oil absorption silica abrasives particularly useful in the practice of the invention are sold under the trade designation Sylodent XWA® Davison Chemical Division of W.R. Grace & Co., Baltimore, Maryland. 21203. Sylodent 650 XWA®, a silica hydrogel composed of colloidal silica particles having a water content of 29% by weight, averaging about 7 to about 10 microns in diameter, and an oil absorption coefficient of less than about 70 cc. cc / 100 g silica is an example of a low oil absorption silica abrasive useful in the practice of the present invention.

Foaming Agents : The oral care compositions of the invention may also include an agent for increasing the amount of foam that is generated when using the brush in the oral cavity. Illustrative examples of agents that increase the amount of foam include, but are not limited to, polyoxyethylene and certain polymers, including, but not limited to, alginate polymers. Polyoxyethylene can increase the amount of foam and the thickness of the foam produced by the oral care carrier component of the present invention. Polyoxyethylene is also commonly known as polyethylene glycol ("PEG") or polyethylene oxide. Polyoxyethylenes suitable for this invention should have a molecular weight of from about 200,000 to about 7,000,000. In one embodiment, the molecular weight is from about 600,000 to about 2,000,000, and in another embodiment, from about 800,000 to about 1,000,000. Polyox® is commercially available. the name of high molecular weight polyoxyethylene manufactured by Union Carbide. Polyoxyethylene may be present in an amount from about 1% to about 90%, in one embodiment from about 5% to about 50%, and in another embodiment from about 10% to about 20% by weight of the oral care carrier component compositions for caring for the oral cavity according to the present invention. If present, the amount of foaming agent in the oral care composition (i.e., single dose) is from about 0.01 to about 0.9% by weight, from about 0.05 to about 0.5% by weight, and in another embodiment, from about 0.1 to about 0.2% by weight.

Surfactants : Compositions useful in the invention may contain anionic surfactants, for example:

i. water-soluble salts of monoglyceride monosulfates of higher fatty acids, such as sodium salt of monosulfate monoglyceride of hydrogenated fatty acids of coconut oil, such as sodium N-methyl N-cocoyl taurate, sodium coco monoglyceride sulfate.

ii. higher alkyl sulfates such as sodium lauryl sulfate.

iii. higher alkyl ether sulfates, for example, with the formula CH ₃ (CH ₂ ) _m CH ₂ (OCH ₂ CH ₂ ) _n OSO ₃ X, where m is 6-16, for example 10, n is 1-6, for example 2 , 3 or 4, and X is Na or K, for example sodium laureth-2 sulfate (CH ₃ (CH ₂ ) ₁₀ CH ₂ (OCH ₂ CH ₂ ) ₂ OSO ₃ Na).

iv. higher alkylaryl sulfonates such as sodium dodecylbenzenesulfonate (sodium laurylbenzenesulfonate).

v. higher alkyl sulfoacetates such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1,2-dihydroxypropanesulfonate, sulphocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate.

By "higher alkyl" is meant, for example, C _6-30 alkyl. In specific embodiments, the anionic surfactant is selected from sodium lauryl sulfate and sodium lauryl sulfate ester. The anionic surfactant can be present in an amount that is effective, for example,> 0.01% by weight of the composition, but not at a concentration that will irritate the tissues of the oral cavity, for example, at <10%, but optimal the concentration depends on the specific formulation and the specific surfactant. For example, the concentrations used for mouthwash are typically on the order of one tenth of that used in toothpaste. In one embodiment, the anionic surfactant is present in the dentifrice in an amount from about 0.3% to about 4.5% by weight, for example, about 1.5%. The compositions of the invention may further comprise mixtures of surfactants, for example containing anionic surfactants and other surfactants, which can be anionic, cationic, zwitterionic or nonionic. Typically, surfactants are substances that are reasonably stable over a wide pH range. Surfactants are described more fully in, for example, US Pat. No. 3,959,458 Agricola et al .; US patent No. 3937807, Havel; and US Pat. No. 4,051,234 to Gieske et al. In some embodiments, anionic surfactants useful herein include water-soluble salts of alkyl sulfates having from about 10 to about 18 carbon atoms in the alkyl radical, and water-soluble salts of sulfonated monoglycerides of fatty acids having from about 10 to about 18 carbon atoms ... Sodium lauryl sulfate, sodium lauryl sarcosinate and sodium monoglyceride sulfonates from coconut are examples of this type of anionic surfactant. In a specific embodiment, the composition according to the invention, for example, Composition 1 et al., Contains sodium lauryl sulfate.

The surfactant or mixtures of compatible surfactants can be present in the compositions of the present invention in an amount of from about 0.1% to about 5.0%, in another embodiment from about 0.3% to about 3.0%, and in another embodiment, from about 0.5% to about 2.0% of the total weight of the composition.

Tartar Prevention Agents : In various embodiments of the present invention, the compositions comprise an anticalculus (tartar prevention) agent. Suitable anticalculus agents include, but are not limited to, phosphates and polyphosphates (eg, pyrophosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinc citrate trihydrate, polypeptides, polyolein sulfonates, polyolein phosphates, diphosphonates. The invention can thus contain phosphate salts in addition to zinc phosphate. In specific embodiments, these salts are alkaline phosphate salts, i. E. salts of alkali metal hydroxides or alkaline earth metal hydroxides, for example sodium, potassium or calcium salts. "Phosphate" as used herein includes orally acceptable mono- and polyphosphates, for example, P _1-6 phosphates, for example, monomeric phosphates such as monobasic, dibasic or tribasic phosphates; dimeric phosphates such as pyrophosphates; and multimeric phosphates such as sodium hexametaphosphate. In specific examples, the selected phosphate is selected from salts of alkaline dibasic phosphate and alkaline pyrophosphate, for example, selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate or more, and a mixture of any two. In a specific embodiment, for example, the compositions comprise a mixture of sodium tetrapyrophosphate (Na ₄ P ₂ O ₇ ), calcium pyrophosphate (Ca ₂ P ₂ O ₇ ) and disubstituted sodium phosphate (Na ₂ HPO ₄ ), for example, in an amount of about 3-4 % sodium phosphate disubstituted and about 0.2-1% each of the pyrophosphates. In another embodiment, the compositions comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP) (Na ₅ P ₃ O ₁₀ ), for example, in a ratio of about 1-2% TSPP and about 7% to about 10% STPP. Such phosphates are provided in an amount effective to reduce enamel erosion, to aid in tooth cleaning and / or to reduce dental calculus on the teeth, for example, in an amount of 2-20%, for example, about 5-15% by weight of the composition.

Fragrances : Compositions for caring for the oral cavity according to the invention may also contain a fragrance. Flavoring agents that are used in the practice of the present invention include, without limitation, essential oils, as well as various flavoring aldehydes, ethers, alcohols and similar materials. Examples of essential oils include spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange oils. Chemicals such as menthol, carvone, and anethole are also helpful. Some embodiments use peppermint and spearmint oils. The flavoring agent can be included in the oral composition at a concentration of from about 0.1 to about 5% by weight, for example, from about 0.5 to about 1.5% by weight.

Polymers : Compositions for caring for the oral cavity according to the invention may also contain additional polymers to adjust the viscosity of the composition or improve the solubility of other ingredients. Such additional polymers include polyethylene glycol, polysaccharides (eg cellulose derivatives, eg carboxymethyl cellulose, or polysaccharide gums, eg xanthan gum or carrageenan gelling agent). Acidic polymers, for example polyacrylate gels, can be in the form of their free acids or partially or completely neutralized water-soluble alkali metals (eg potassium and sodium) or ammonium salts.

Silica thickeners may be present and form polymer formulations or gels in aqueous media. It should be noted that these silica thickeners are physically and functionally different from the silica particles also present in the composition because the silica thickeners are very fine and provide little or no abrasion. Other thickeners are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, and water-soluble cellulose ether salts such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic and gum tragacanth can also be included. Colloidal magnesium aluminum silicate can also be used as a component of a thickening composition to further improve the texture of the composition. In some embodiments, thickeners are used in an amount of from about 0.5% to about 5.0% by weight of the total composition.

Compositions of the invention may include an anionic polymer, for example, in an amount of about 0.05 to about 5%. Such substances are known to be primarily used in dentifrices, although not for this particular application useful in the present invention, are disclosed in US Pat. Nos. 5,188,821 and 5,192,531; and include synthetic anionic polymeric polycarboxylates such as 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether / maleic anhydride, having a molecular weight (M.W.) of about 30,000 to about 1,000,000, most preferably from about 300,000 to about 800,000. These copolymers are available, for example, as Gantrez., for example, AN 139 (M.W. 500,000), AN 119 (M.W. 250,000), and preferably pharmaceutical grade S-97 (M.W. .W. 700000) is available from ISP Technologies, Inc., Bound Brook, NJ 08805. Enhancers, if present, are present in amounts ranging from about 0.05 to about 3% by weight. Other useful polymers include those such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrolidone or ethylene, the latter being available, for example, as Monsanto EMA No. 1103, M.W. 10,000 and EMA quality 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Typically suitable are polymerized olefinic or ethylenically unsaturated carboxylic acids containing an activated carbon-carbon olefinic double bond and at least one carboxyl group, i.e. an acid containing an olefinic double bond that readily functions in polymerization from- for its presence in the monomer molecule either in the alpha or beta position relative to the carboxyl group or as part of a terminal methylene group. Illustrative examples of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesoconic, alphaconitic 2 -benzyl acrylic, 2-cyclohexyl acrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other excellent olefinic monomers copolymerizable with such carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. Copolymers contain sufficient carboxyl salt groups to be water soluble. Another class of polymeric substances includes a composition containing homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and salts thereof, in particular where the polymers are based on unsaturated sulfonic acids selected from acrylamido alikanoic sulfonic acid such as 2-acrylamide-2-methylpropanesulfonic acid, having a molecular weight of about 1,000 to about 2,000,000, described in US Pat. No. 4,842,847, June 27, 1989 to Zahid. Another useful class of polymeric agents includes polyamino acids containing ratios of anionic surfactant amino acids such as aspartic acid, glutamic acid and phosphoserine, for example, as disclosed in US Pat. No. 4,866,161 to Sykes et al.

Water : Oral compositions can include significant amounts of water. The water used in the preparation of commercial oral care compositions must be deionized and free of organic impurities. The amount of water in the composition includes free water that is added, plus the amount that is added with other materials.

Humectants : In certain embodiments of the oral care compositions, it is also desirable to include a humectant to prevent the composition from hardening upon exposure to air. Certain humectants can also impart desirable sweetness or aroma to the dentifrice composition. Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol, and other polyols and mixtures of these humectants. In one embodiment, the main humectant is glycerin, which may be present at levels greater than 25%, eg, 25-35%, about 30%, with 5% or less other humectants.

Other Optional Ingredients : In addition to the components described above, embodiments of the present invention may contain various optional dentifrice ingredients, some of which are described below. Optional ingredients include, for example, but are not limited to adhesives, foaming agents, flavors, sweeteners, anti-plaque agents, abrasives, and colorants. These and other optional components are further described in US Pat. No. 5,004,597 to Madjeti; US patent No. 3959458 Agricola et al. and US Pat. No. 3,937,807 to Havel, each of which is incorporated herein by reference.

As used throughout, ranges are used as an abbreviation to describe each and every value that falls within a range. Any value within the range can be selected as the end of the range. In addition, all references cited herein are incorporated by reference in their entirety. In the event of a conflict between a definition in the present disclosure and that of a cited reference, the present disclosure is determinative.

Unless otherwise indicated, all percentages and amounts expressed in this document and elsewhere in the specification are to be understood as percentages by weight. Amounts quoted are based on the active weight of the material.

EXAMPLES

Example 1

A test dentifrice was prepared containing 2% zinc phosphate combined with 5% arginine, 1450 ppm fluoride, and phosphates. This dentifrice has a pH of 9.13, corresponding to a relatively high arginine content. Dentifrices containing 2% zinc citrate, 1% zinc citrate, 1% zinc citrate + 1% zinc phosphate, zinc or arginine free, are also prepared according to the following formulations (ingredients by weight of the composition):

Example 2

The dentifrice of Example 1 containing 2% zinc phosphate, together with arginine and fluoride, was highly acidic compared to a control dentifrice containing 1% zinc citrate.

The in vitro methodology is used to determine the enamel protection activity of the prototype compositions according to example 1. Enamel substrates (N = 6/8 per cell) are prepared by introducing cattle incisors into a polymer based on methacrylate and sequential polishing using 600 and 1200 grit carbide paper ... Take care not to penetrate the dentin layer when polishing the enamel to a mirror finish. Before testing, all enamel substrates are pre-etched with 5% citric acid for 30 seconds. Half of the side of each substrate is masked with acid resistant tape to protect the surface as a reference surface. In the model used for product evaluation, a 1-min product treatment period was alternated with 2-min acid treatment periods in accordance with the constant sequence T-C-C-C-C-T (T = product treatment, C = acid attack). Acid treatment is performed using a 1% aqueous citric acid solution (unbuffered) adjusted to a pH of 3.8 with NaOH. All enamel substrates are stored in sterile artificial saline at 37 ° C at a time when not exposed to processing or exposure. This regime is carried out for a total of five days, at the end of which a microhardness test is applied to quantify the enamel lost due to erosion on each enamel substrate on protected and exposed surfaces. The percentage change in hardness is calculated. Without treatment, using deionized water instead of the test dentifrice, the change in percent hardness is very high, approaching 80%, with little variation from experiment to experiment depending on the specific substrate.

The 2% zinc phosphate formulation is effective at demineralization in this in vitro model with pH cycles to study the protective effect of treatments on early enamel dissolution, with a decrease in hardness after repeated acid exposure by only 24.3%, which is less than a decrease a hardness of 26.3% observed with a 1% zinc citrate formulation. A separate experiment shows that increasing the amount of zinc citrate in the formulation from 1% to 2% does not lead to an increase in acidic effectiveness. The maximum effect is achieved already at 1%. Thus, the effectiveness of the zinc phosphate formulation in this test is superior or at least no worse than the maximum effect achieved with the zinc citrate formulation, which is surprising in light of the current opinion in the art that zinc phosphate is relatively inert. in the mouth.

Additional experiments were conducted to evaluate formulations containing zinc phosphate (ZnP) with and without arginine and formulations containing 1% zinc phosphate and zinc citrate. A commercial enamel-protective toothpaste (Commercial 1) containing sodium fluoride and potassium nitrate is included as a positive control. (Note: preparations made from different human teeth are used for each series of experiments, so there may be some differences between the series of experiments):

table 2 Without processing ZnP ZnP + Zinc Citrate ZnP + Arg Commercial 1 % Reduction in hardness 67.56 34.13 44.19 31.26 32.96

In these series of experiments, zinc phosphate with arginine is at least as good as the positive control, and surprisingly, is significantly better than the combination of zinc phosphate and zinc citrate.

Example 3

Electronic Spectroscopy for Chemical Analysis (ESCA, also known as X-ray Photoelectron Spectroscopy or XPS) is a surface analysis technique used to obtain chemical information about the surfaces of solid materials. The material characterization method uses an X-ray beam to excite a solid sample, resulting in the emission of photoelectrons. Energy analysis of these photoelectrons provides both elemental and chemical binding information on the sample surface. The relatively low kinetic energy of photoelectrons gives the ESCA a sample with a depth of about 30 Å. ESCA is used to analyze the mineral composition of enamel before and after application of the test versus control dentifrices on polished and etched enamel substrates prepared and treated as described in the examples above, confirming that zinc is delivered to the enamel surface and that zinc remains on surfaces even after acidic exposure, as well as confirming the effective delivery of fluoride.

The ESCA data for enamel samples treated with various Zn / arginine / phosphate anti-erosion pastes of Example 1 are shown in Table 3 below, which lists the detected elements and their corresponding atomic concentrations. All samples are analyzed after each stage of polishing, etching and processing. For simplicity, only the average composition for all samples is presented for the polished and etched surface. In all cases, three to four separate zones are analyzed for each sample. For the processed samples, the compositions of the individual regions are presented, as well as the average composition for each sample.

C and N are detected on polished and etched samples from surface organics. Ca and P are detected from hydroxylapatite (HAP) in enamel, with a P / Ca ratio typical of enamel surfaces. The average P / Ca ratio for the etched surface is slightly lower than for polished surfaces, which indicates a decrease in surface phosphate relative to Ca that occurs after etching. Low zinc levels are detected for polished surfaces, which are removed by etching. Fluoride is also detectable on both polished and etched surfaces at low levels. Low Na levels are also observed. In general, the compositions of polished and etched enamel surfaces are typical of bovine enamel.

C and N are detected on the surface of all processed samples from surface organics. The C levels for all samples are higher than those for etched surfaces, due to the presence of residual organic matter, most likely from the paste. N levels are also higher for the test samples relative to etched surfaces.

Ca and P are also detectable on sample surfaces, from HAP to enamel. The P / Ca ratios for the studied samples are higher than for that of the etched surfaces, which indicates an excess of phosphate in relation to Ca. For all samples, the Na concentration is also significantly higher than that of the etched enamel. Higher levels of phosphate and Na in the treated samples indicate that the Na phosphate from the paste is deposited on the enamel surfaces. Si is also detected in low amounts on treated enamel, due to residual silicon dioxide from the paste.

For enamel specimens treated with pastes containing zinc citrate or zinc phosphate, elevated levels of zinc are observed at the surface. As for previous studies, Zn / Ca ratios are the best way to compare the absorption of zinc on the enamel surface. The Zn / Ca ratio for enamel treated with zinc phosphate paste is higher than for zinc citrate pastes. This means that zinc phosphate paste deposits more zinc on the enamel than zinc citrate products. On a mole basis, zinc phosphate contains more zinc than an equal amount of zinc citrate by weight. This may explain the greater amount of zinc detected on enamel treated with zinc phosphate paste, but in any case, it is clear that zinc phosphate is effective in delivering zinc to the enamel surface. Overall, the Zn / Ca ratios observed for the samples in the present study are about twice that of the enamel samples from the previously reported pH cycling study.

ESCA zinc peak positions can provide information on the chemical state of zinc on the enamel surface. The positions of the zinc peaks for all samples treated with zinc-containing pastes are the same. This suggests that zinc present in all samples is in a similar chemical form. In addition, the positions of the zinc peaks for samples treated with zinc paste are the same as for background zinc on polished enamel surfaces. The background zinc, inherently present in enamel, is probably in the form of zinc HAP. Thus, the data suggest that zinc on treated enamel may also be in the form of zinc HAP.

F in the form of fluoride is detected on the surfaces of all enamel samples treated with pastes. The relative absorption of fluoride between samples is also better defined using the Zn / Ca ratios. The data obtained indicate that enamels treated with pastes with 1% and 2% zinc citrate had similar Zn / Ca ratios, which suggests a similar absorption of F. Enamel treated with pastes with zinc citrate without arginine and Ζn ₃ (ΡO ₄ ) ₂ shows slightly lower Zn / Ca ratios than other samples. The lower fluoride uptake for the last two treatments is, however, within normal variation for this type of study.

ESCA results indicate that zinc deposition occurs for enamel treated with pastes containing either zinc citrate or zinc phosphate. Zinc deposition is greater for zinc phosphate pastes compared to zinc citrate pastes. The data obtained also suggest that zinc may be present on the surface in the form of zinc-HAP. Elevated fluoride levels are also observed for all paste-treated samples.

Detailed analysis results are presented in Table 3 (below).

As these data show, the delivery of zinc to enamel using the zinc phosphate formulation (mean 0.58) is in fact higher than the delivery of zinc using any of the zinc citrate formulations. The incorporation of zinc into enamel, possibly through the composition of the material with zinc hydroxyapatite, is beneficial in view of the beneficial effects of zinc in controlling erosion and reducing bacterial biofilm deposition. The delivery of fluoride with the zinc phosphate formulation is also within the acceptable range, showing significant fluoride deposition compared to the control, similar to the zinc citrate formulation without arginine.

Example 4

Although zinc phosphate is insoluble in water, it has been found to be soluble in acidic solutions. Compositions containing, for example, 2% lactic acid (approx. PH 2.4), or even at least 0.05% citric acid (approx. PH 4), with 0.01-0.03% zinc phosphate do not show precipitation. It has been found that the solubility of zinc phosphate can be increased in a formulation containing an amino acid and / or a betaine surfactant. A stable mouthwash is presented as follows:

Ingredient Weight % Sorbitol 5.5 Glycerol 7.5 Propylene glycol 7 Sodium saccharin 0.02 Citric acid (anhydrous) 0.05 Zinc phosphate 0.028 Flavor / colorant 0.12 Potassium sorbate 0.05 Cocamidopropyl betaine one Water QS Total 100

Claims (6)

1. A dentifrice containing from 1 to 3% by weight of zinc phosphate, where zinc phosphate is added to the dentifrice as a preformed salt, and arginine in free or orally acceptable salt form in an amount from 1 to 8% weight, from 2 to 8% by weight of an alkaline phosphate salt selected from sodium phosphate dibasic, potassium phosphate dibasic, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate and a mixture of any two or more of these, from 700 to 2000 hours per million fluoride in a silica-based dentifrice. 2. A dentifrice according to claim 1, comprising one or more humectants and one or more surfactants. 3. A dentifrice according to claim 1 or 2, further comprising an effective amount of one or more antibacterial agents. 4. A dentifrice according to claim 1 or 2, further comprising a whitening agent. 5. The dentifrice of claim 1 or 2 further comprising one or more zinc ion sources in addition to zinc phosphate. 6. A dentifrice according to claim 1 or 2, wherein the pH of the composition is alkaline.